Mario Götze and Paco Alcácer will not be involved for Borussia Dortmund on Saturday after failing to make the trip to Berlin.
The news was broken by Ruhr Nachrichten and leaves the Black and Yellows without many options. Fellow forward Maximilian Philipp is already out through injury.
Götze and Alcácer have scored a combined 18 Bundesliga goals this season, with Götze assisting a further six.
Marco Reus, usually stationed behind the main forward, is now expected to lead the line at the Olympiastadion.
Dortmund are also without Axel Witsel, who is likely to be replaced in midfield by Julian Weigl.
According to Bild, Mahmoud Dahoud is expected to join Weigl in midfield.
For the majority of the season, Favre has opted to play a 4-2-3-1 formation. That has become a 4-1-4-1 in recent weeks and he may be forced to retain that shape with so few forwards available.
With Reus up front alone, there will be a huge onus on Jadon Sancho to support him in the final third.